Netherton syndrome

Netherton syndrome (also known as Comèl-Netherton syndrome) is a rare, severe autosomal recessive skin disorder caused by mutations in the SPINK5 gene, which encodes the serine protease inhibitor LEKTI (lympho-epithelial Kazal-type-related inhibitor). This protein plays a critical role in regulating proteases involved in skin barrier formation and desquamation. Loss of LEKTI function leads to unopposed protease activity in the epidermis, resulting in a profoundly defective skin barrier from birth. The condition classically presents with a triad of features: ichthyosiform erythroderma (generalized red, scaly skin), a specific hair shaft abnormality called trichorrhexis invaginata (also known as 'bamboo hair,' where the hair shaft telescopes into itself creating characteristic nodular swellings), and atopic manifestations. Affected newborns often present with congenital ichthyosiform erythroderma, which can be life-threatening due to excessive fluid loss, electrolyte imbalances, temperature instability, and susceptibility to infections. As children grow, the skin may evolve to show ichthyosis linearis circumflexa, a distinctive migratory pattern of polycyclic, double-edged scaling plaques. Hair is typically sparse, short, and brittle across the scalp, eyebrows, and eyelashes. Severe atopic features including eczema, elevated serum IgE, food allergies, allergic rhinitis, and asthma are common. Failure to thrive and recurrent skin infections are frequent complications in infancy and childhood. Affected individuals may also experience hypernatremic dehydration and enteropathy. There is currently no cure for Netherton syndrome. Management is primarily supportive and symptomatic, focusing on intensive skin moisturization with emollients, careful management of infections, nutritional support, and treatment of atopic manifestations. Topical calcineurin inhibitors (tacrolimus, pimecrolimus) may be used with caution, though systemic absorption can be increased due to the impaired skin barrier. Topical corticosteroids must also be used cautiously for the same reason. Intravenous immunoglobulin (IVIG) has been reported to provide benefit in some patients. More recently, dupilumab and other biologic therapies targeting the atopic/inflammatory pathway have shown promise in case reports and small series. Genetic counseling is recommended for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Netherton syndrome